Self-Replicating, Self-Designing DNA Devices

Abstract

It is a grand challenge to understand how to chemically engineer systems which have the self-assembled, dynamic structure and the directed information flow of even the simplest biological cells.Nanoconstruction with synthetic DNA offers an opportunity to meet these challenges.The hybridization rate and bound structure of two DNA molecules can be predicted with reasonable accuracy and we can build 2- and 3-dimensional structures by creating branched DNA junctions.These attributes allow us to design DNA assembly reactions with hundreds of distinct species which together perform complex self-assembly and information processing tasks.

Perhaps the most fundamental biological mechanism is sequence replication and Darwinian evolution.In biology, replication of a DNA sequence is catalyzed by a processive enzyme.I'll describe how by we can engineer an autonomous, enzyme-free system to replicate sequences written in a chemical alphabet consisting of DNA crystal monomers. These monomers consist of short oligonucleotides self-assembled into brick shapes with 4 single stranded "sticky ends" that hybridize to other monomers; repeated hybridization forms 2-dimensional rectangular lattices.The sticky end sequences control the affinity of monomers for other monomer types, and new monomers can be designed by designing the component oligonucleotides, much like designing a set of molecular jigsaw puzzle pieces.I've synthesized a set of monomers that grow into ribbon shaped crystals bearing a "banding pattern" of monomer types, a chemical sequence, that is propagated as the ribbons extend at their ends.We can grow ribbons with a specified initial sequence from engineered nuclei and control the mutation rate and spontaneous generation rate of ribbons by designing the crystal monomers so that information copying during growth is "proofread."We can replicate the sequences using fluid flow, which breaks crystals into multiple pieces that are each able to propagate the initial banding pattern.These crystal have complex patterns that could be used as templates for waveguides or protein arrays.

The cytoskeleton creates dynamic, adaptive structure in eukaryotic cells.Structure is based on local rules rather than a global description and can readily grow or adapt to changes in the environment.I'll describe some early work toward creating a DNA-based "cytoskeleton" consisting of DNA nanotube filaments.One basic construction primitive is the assembly of filaments such that they bridge fixed start and destination points.I'll show how we can template the growth of filaments from a "start" chemical marker, how growing filaments could attach to a "finish" marker, and briefly discuss how we could use this system to create self-guiding wires.

Speaker Biography

Rebecca Schulman is a Miller Research Fellow in the physics department at the University of California Berkeley.She received undergraduate degrees in computer science and mathematics from MIT and received her PhD in 2007 from Caltech where she studied under Erik Winfree.Her research is focused on using synthetic DNA to create materials with nanoscale features that are capable of dynamic reorganization.